Riemersma (NCT00235911).

Methods	Study Design: Randomised, open‐label, active control, parallel assignment, efficacy study. August 2003 to September 2006 Effects of Symbicort single inhaler therapy on bronchial hyper responsiveness, asthma control and safety in mild to moderate asthmatics in general practice, compared to usual care therapy. The primary objective is to compare the effects of Symbicort SiT and treatment according to NHG‐guidelines on bronchial hyper responsiveness in asthmatic patients, as measured by PD20 histamine, and to validate the Bronchial Hyperresponsiveness Questionnaire (BHQ). Two research centres in the Netherlands.
Participants	102 adults enrolled with mild to moderate persistent asthma Inclusion Criteria: diagnosis of mild to moderate asthma, FEV1 > 60% of predicted normal values pre‐bronchodilator, daily use of IGCS during the last 3 months (either up to 800µg/day with LABA or 1600µg/day (BDP equivalence)) mean daily ICS dose at baseline was 770 µg/day (BDP equivalence) there was no requirement for patients to be poorly controlled to be enrolled in this study and mean predicted FEV1 in this study was nearly 100% Exclusion Criteria: Regular need of > 4 inhalations of a short‐acting b2‐agonist/day, known or suspected hypersensitivity to any of the investigational drugs or inhaled lactose, use of any beta‐blocking agent, having smoked >10 pack‐years
Interventions	Budesonide/formoterol 80/4.5 µg two inhalations in the evening and as required for symptom relief Treatment according to GINA guidelines
Outcomes	Primary Outcome Measures: Change in PD20 histamine Secondary Outcome Measures Number of asthma‐control days Time to first mild asthma exacerbation Number of mild asthma exacerbation days Asthma symptom scores (day and night) FEV1 PEF (morning and evening) Number of inhalations with ICS Mean dose of ICS Definition of severe exacerbation Not specified Additional Data Data on file from AstraZeneca indicate that no patients were hospitalised, and 2/54 compared to 6/48 patients had at least one course of oral steroids on SMART and current best practice respectively
Notes	Reported in full for the 2013 update
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No details
Allocation concealment (selection bias)	Unclear risk	No details
Blinding (performance bias and detection bias) All outcomes	High risk	Open‐label study
Incomplete outcome data (attrition bias) All outcomes	High risk	8/54 (15%) discontinued on SiT and 4/48 (8% discontinued on usual care.
Selective reporting (reporting bias)	Low risk	Data have been obtained for all primary outcome measures